Deep brain stimulation system for the treatment of parkinson&#39;s disease or other disorders

ABSTRACT

A deep brain stimulation (DBS) system ( 10 ) provides a multiplicity of stimulation channels through which stimulation may be delivered deep within the brain of the patient. The DBS system is powered by a rechargeable battery ( 27 ). In one embodiment, the system has four channels driving sixteen electrodes ( 32 ). The DBS system is easily programmed fur use by a clinician using a clinician programming system ( 60 ), and further affords a simple but highly advanced hand held programmer ( 50 ) control interface through which the patient may easily change stimulation parameters within acceptable limits. The DBS system ( 10 ) includes a small, implantable pulse generator ( 20 ) that is small enough to be implanted directly in the cranium of the patient, thereby eliminating the long lead wires and tunneling procedures that have been used in the past. Further, the DBS system allows up to two electrode arrays ( 30, 30 ′) to be attached to the implantable pulse generator ( 20 ), thereby eliminating the requirement for implanting two independent implantable pulse generators for bilateral stimulation of deep brain structures.

BACKGROND OF THE INVENTION

[0001] The present invention relates to deep brain stimulation (DBS)systems, and more particularly to a DBS system that utilizes amultichannel implantable pulse generator (IPG) small enough to beimplanted directly in the cranium of the patient

[0002] More than a decade ago, a single channel implantable pulsegenerator (IPG) was developed for the purpose of stimulating the spinalcord to treat chronic and intractable pain. Over the years, more andmore applications for implantable systems that could deliver electricalstimulation to neural tissues were discovered, including the stimulationof structures deep within the brain controlling movement. For each ofthese applications, the single channel IPG with it's single channelstimulator was placed into a new package, sometimes with a new name,sometimes with a variation in its electrode, and provided as a newproduct, each time using the same electronics, power systems, telemetrymethods, cumbersome programming methods, and often the same leadwiresand surgical tools for those devices. So, while the technology offeredthrough the single channel device was not as sophisticated as what itcould deliver, it was still the best available technology, and as aresult systems have existed that may not have been adequate for the job,but were better than no systems as all.

[0003] There is now a recognition that patients suffering fromParkinson's Disease, essential tremor, and other movement disorders,need better devices to treat their conditions. Such devices need to lastmany times longer, need to reduce the surgical time required for theirimplantation, and need to better address the problems for which they areapplied in patients. Moreover, such devices should preferably bedesigned for the surgical location of the device and the structures tobe stimulated, rather than just be a re-labeled system designed foranother application altogether and simply marketed for a newapplication.

[0004] Thus, while single channel DBS systems are known in the art, suchsystems suffer from numerous defects and serious deficiencies.

[0005] For example, one system used today for DBS applications utilizesan implantable pulse generator powered by a primary battery(non-rechargeable), originally designed for spinal cord stimulation. Thepulse generator is large and must be implanted in the shoulder region,thereby requiring long leads and an arduous surgical procedure oftunneling in order to interconnect the leads with the pulse generatorand in order to place the leads and electrodes in the desired locationin contact with brain tissue. For many patients with aggressivestimulation parameter settings, the lifetime of the primary battery isvery short, thus requiring frequent replacement surgeries.

[0006] An alternative to the primary battery powered device is anRF-powered device which requires that the patient wear an antenna coilover the site of the implant and carry an externaltransmitter/controller.

[0007] When bilateral stimulation is required using existing DBSdevices, which occurs often, two complete, independent pulse generators,including separate lead wires and electrode systems must presently beimplanted.

[0008] Patient controllers for use with existing systems require thatthe patient controller be held directly over the implant site for thetransfer of telemetry commands. This makes use of such patientcontroller for an implant site on the cranium extremely difficult, ifnot impossible. Additionally, use of such a patient controller with ashoulder-located stimulator is similarly deficient.

[0009] It is thus seen that numerous problems and deficiencies arepresent with existing DBS systems.

[0010] A brief review of the literature follows which describes the workof various clinicians and researchers in the application of DBS andearly chronic cerebellar stimulation (CCS) for the treatment of pain andmovement disorders. Basic research and issues with the technology ofelectrical stimulation are discussed.

[0011] CCS and DBS Early Work

[0012] Cooper, I, in various publications made in 1978, 1980, 1981, and1984, (see, erg., Cooper, I: Historical review of cerebellarstimulation. Cerebellar Stimulation for Spasticity and Seizures: 3-8,1984 by Davis, R and Bloedel, J), reported that chronic cerebellarstimulation (CCS) and deep brain stimulation (DBS) were employed toreverse some of the symptoms of spasticity, hemiparesis, tremor,dystonia and torticollis by prosthetic mobilization of CNS inhibitorymechanisms in the cerebral cortex and thalamus. Again, in 1985, Cooperdemonstrated that the long term chronic stimulation of the brain hasresulted in no harmful effects in any case while at the same timedemonstrating effectiveness (see Cooper et al., “The effect of chronicstimulation of cerebellum and thalamus upon neurophysiology andneurochemistry of cerebral cortex”, Neurostimulation: An Overview:207-212, 1985 by Lazorthes, Y and Upton, A.) Others had previouslyshown, in a double blind study, the efficacy of cerebellar stimulationfor spasticity (see, e.g., McLellan, D et al., “Time course of clinicaland physiological effects of stimulation of the cerebellar surface inpatients with spasticity”, Journal of Neurology 41, 150-160, 1978).

[0013] Bilateral DBS

[0014] It has recently been demonstrated that Bilateral DBS of theinternal pallidum and the subthalamic nucleus improves a number ofaspects of motor function, movement time, and force production, with fewsignificant differences between internal pallidum and subthalamicnucleus groups; and that the effects are similar to unilateral pallidallesions reported elsewhere (see, Brown, R. G. et at, “Impact of deepbrain stimulation on upper limb akinesia in Parkinson's disease”, Annalsof Neuology, 45(4)473-487, April 1999.) One year earlier, in 1998, RKumar reported on one of the few double blind studies that objectivelyverified the clinical effects of subthalamic nucleus (STN) DBS inadvanced Parkinson's Disease (PD) (see Kumar, R, et. al., “Double-blindevaluation of subthalamic nucleus deep brain stimulation in advancedParkinson's disease”, Neurology, 51:850-855, 1988). Kumar's conclusionswere that STN DBS is a promising option for the treatment of advanced PDand that the clinical benefits obtained outweighed the adverse effects.Later, Kumar also looked at bilateral globus pallidus internus (GPi) DBSfor medication-refractory idiopathic generalized dystonia, and reportedobtaining good results (see, Kumar et al., “Globus pallidus deep brainstimulation for generalized dystonia: clinical and PET investigation”,Neurology, 53:871-874, 1999).

[0015] It has also been demonstrated that bilateral DBS inlevodopa-responsive patients with severe motor fluctuations was safe andefficient (see, Ghika, J. et al., “Efficiency and safety of bilateralcontemporaneous pallidal stimulation (deep brain stimulation) inlevodopa-responsive patients with Parkinson's disease with severe motorfluctuations: a 2-year follow-up review”, J. Neurosurg., Vol. 89,pp713-718, November 1998). In this report, Ghika indicated thatimprovements in motor score Activities of Daily Living (ADL) wereobtained, and that off time persisted beyond two years after theoperation, but that signs of decreased efficacy started to be seen after12 months. Siegfried, J confirmed in 1994 that the use of bilateral DBSfor PD was both nondestructive and reversible (Siegfried, J. et al.,“Bilateral chronic electrostimulation of ventroposterolateral pallidum:a new therapeutic approach for alleviating all Parkinsonian symptons”,Neurosurgery, 35(6):1126-1130, December 1994).

[0016] Unilateral DBS

[0017] Good results have also been demonstrated with unilateral thalamicDBS for refractory essential (ET) and Parkinson's Disease (PD) tremor,with 83% and 82% reductions respectively in contralateral arm tremor(see, Ondo W, et al., “Unilateral thalamic deep brain stimulation forrefractory essential tremor and Parkinson's disease tremor”, Neurology,51:1063-1069, 1998). However, no meaningful improvement in other motoraspects was observed.

[0018] Unilateral and Bilateral Pallidotomy

[0019] In 1998, the results of unilateral ventral medial pallidotomy wasreviewed in 22 patients at 3 months postoperatively and at 14 months(see, Schrag A, et al., “Unilateral pallidotomy for Parkinson's disease:results after more than 1 year”, J. Neurol Neurosurg Psychiatry,67:511-517, 1999). It was concluded that the beneficial effects persistfor at least 12 months, and that dyskinesias are most responsive to thisprocedure. The reduction of contralateral dyskinesias was, however,slightly attenuated after 1 year. Another study, involving 21 patients,demonstrated that the pain associated with PD can be significantlyreduced with unilateral pallidotomy (see, Honey et al., “Unilateralpallidotomoy for reduction of Parkinsonian pain”, J Neurosurg.91:198-201, 1999). Earlier, other researchers had demonstrated controlof levodopa-induced dyskinesias by thalamic lesions delivered bymicroelectrode technique and controlled in size and accurately locatedwith respect to ventralis oralis (Vo) complex and ventralis intermediatenucleus (Vim) (see, Narabayashi, et al., “Levodopa-induced dyskinesiaand thalamotomy”, J. Neurology, Neurosurgery, and Psychiatry 47:831-839,1984).

[0020] R M Scott et al. (Scott et al., “The effect of thalamotomy on theprogress of unilateral Parkinson's disease”, J Neurosurg, 32:286-288,Mar. 1970) reviewed 72 patients exhibiting long term post unilateralthalamotomy to determine whether the procedures were adequate. Theirresults indicated, as suggested previously by Cooper, that unilateralprocedures were inadequate and that when symptoms were absent from theside not receiving the procedure, they often appeared later when theywere no longer benign. E Levita (Levita et al., “Psychologicalcomparison of unilateral and bilateral thalamic surgery”, Journal ofAbnormal Psychology 72 (3), 251-254, 1967) reported no significantdifferences between unilateral versus bilateral thalamic surgery incognitive and perceptual functions and performance on visual andauditory tasks of recent recall.

[0021] DBS and Effects on Memory, Other Functions

[0022] One group of researchers suggested that in the application ofchronic DBS of the left ventrointermediate (Vim) thalamic nucleus forthe treatment of PD on semantic (verbal fluency and confrontationnaming) and episodic (word list) memory tasks that DBS might interferewith access to episodic memory, but enhance access to semantic memory(see, Troster et al., “Chronic electrical stimulation of the leftventrointermediate (Vim) thalamic nucleus for the treatment ofpharmacotherapy-resistant Parkinson's disease: a differential impact onaccess to semantic and episodic memory?”. Brain and Cognition,38:125-149, 1998). Troseter et al., suggested that future studies lookat effects of number and locations of electrodes. Earlier, it had beenreported that thalamic stimulation and thalamotomy had been utilized tostudy the H reflex (Laitinen et al., “Effects of thalamic stimulationand thalamotomy on the H reflex”, Electroencephalography and ClinicalNeurophysiology 28:586-591, 1970). Laitinen's report found that the Hreflex was facilitated by repetitive stimulation of the contralateralVL, while coagulation of VL diminished the H reflex in half of thepatients, suggesting that there are at least two different pathways fromthe VL area which facilitate the spinal motoneurone.

[0023] Another report indicated that in five PD patients with “freezing”gait and postural instability, chronic unilateral DBS of the STNresulted in effectively alleviating this gait with improvement inwalking in all of the patients tested (see, Yokoyama et al.,“Subthalamic nucleus stimulation for gait disturbance in Parkinson'sdisease”, Neurosurgery, 45(1):41-49, July 1999). STN stimulation wasalso reported by other researchers to alleviate akinesia and rigidity inPD patients (Pollak et al., “Subthalamic nucleus stimulation alleviatesakinesia and rigidity in Parkinsonian patients”, Adv Neurology,69:591-594, 1996).

[0024] Pain, Device Failures, Issues in Implementing the Technology

[0025] It has been reported that parafasicular-center median nucleistimulation for intractable pain and dyskinesia and thalamic stimulationfor chronic pain have been successful. (Andy O J, “Parafascicular-centermedian nuclei stimulation for intractable pain and dyskinesia(painful-dyskinesia)”, Appl. Neurophysiol., 43:133-144, 1980; Dieckmannet al., “Initial and long-term results of deep brain stimulation forchronic intractable pain”, Appl. Neurophysiol., 45:167-172, 1982).Additionally, the notion of two separate sensory modulating system wassupported through the combined stimulation of the periaqueductal graymatter and sensory thalamus (Hosobuchi, Y “Combined electricalstimulation of the periaqueductal gray matter and sensory thalamus”,Applied Neurophysiology 46:112-115, 1983).

[0026] G H Duncan (Duncan et al., “Deep brain stimulation: a review ofbasic research and clinical studies”, Pain 45:49-59, 1991) reviewed 30years of DBS for pain and concluded that there is considerable evidence,in both basic and clinical studies, suggesting that deep brainstimulation can modify the activity of nociceptive neurons, and thatthis approach should be a feasible alternative for the treatment ofchronic, intractable pain. Duncan suggested that future research beconstrained to primates, rather than in cats and rats to narrow thedifferences between basic and clinical studies and that overall, studieswith mixed results appear to have poor controls without the benefit ofrigorous experimental standards.

[0027] K. Kumar (Kumar et al., “Deep brain stimulation for intractablepain: a 15-year experience”, Neurosurgery, 40(4):7360747, 1997) followed68 patients over 15 years and noted long term effective pain controlwith few side effects or complications. R. R. Tasker (Tasker et al.,“Deep brain stimulation for neuropathic pain”, Stereotack Funct.Neurosurg., 65:122-124, 1995) investigated the use acommercially-available electrode and stimulator, available from awell-known medical equipment manufacturer, for DBS for the treatment ofpain. In his investigation, 62 patients were tested, and 25 patientsimplanted of paresthesia-producing (PP) and periventricular gray (PVG)were evaluated. In no case did PVG DBS produce pain relief: in 15 PPpatients, some pain relief was produced. Of particular note were theproblems associated with the use of the device: 2 cases of seizures dueto migrated electrodes, 14 other electrode migrations, 2 receivermigrations, 1 receiver malfunction and 8 general equipment breakages,disconnections or extrusions.

[0028] R. M. Levy (Levy et al., “Treatment of chronic pain by deep brainstimulation: long term follow-up and review of the literature”,Neurosurgery, 21:6, 885-893, 1987) reported on the long term follow-upof treatment of chronic pain with DBS of 141 patients having a meanlength of follow-up of 80 months post implant. Technical problems mostoften encountered included migration of the implanted electrodes andequipment failure that led to leakage of current and ineffectivestimulation. Lasting relief from pain was obtained in 47% of patientswith deafferentiation and 60% with nociceptive pain. Caparros-Lefebvre(Caparros-Lefebvre et al., “Improvement of levodopa induced dyskinesiasby thalamic deep brain stimulation is related to slight variation inelectrode placement: possible involvement of the centre median andparafascicularis complex”, J. Neurol. Neurosurg. Psychiatry, 67:308-314,1999) investigated why two teams using the same procedure and the sametarget for DBS obtained different results on levodopa induceddyskinesias, whereas Parkinsonian tremor was improved or totallysuppressed, and it was discovered that there was on average electrodeplacement difference of 2.9 mm in electrode depth, which did not seem tocorrespond to the coordinates of the VIM, but rather seemed to be closerto those of the centre median and parafascicularis (CM-Pf) complex TheCaparros-Lefebvre study seems to support the hypothesis that patientsexperiencing an improvement of dyskinesias under DBS are actuallystimulated in a structure which is more posterior, more internal anddeeper than the VIM, very dose to the CM-Pf. However, J. Guridi (Guridiet al., “Stereotactic targeting of the globus pallidus internus inParkinson's disease: imaging versus electrophysiological mapping”,Neurosurgery, 45(2):278-289, August, 1999) determined that lesiontargeting based on MRI alone is not sufficiently accurate to guaranteeplacement of the lesion in the sensorimotor region of the globuspallidus internus (Gpi).

[0029] J. Miles (Miles et al., “An electrode for prolonged stimulationof the brain”, Applied Neurophysiology 45:449-455, 1982) describedseveral of the problems with the electrode used in the Kumar study: 1)electrode roughness presents a danger of trauma along the cannula track;2) definite risk of early displacement of the electrode tip from itstarget site, especially with the electrode is disengaged from theinsertion tool, because the intrinsic springlike behavior of theelectrode tends to cause it to retract along its insertion track; 3)displacement of the electrode tip from its insertion position can alsooccur over a period of time, presumably due to the dynamic pulsatilenature of the brain; 4) repositioning of an electrode which is notproducing satisfactory stimulation effects is difficult because of theprogressively increasing distortion and springlike behavior of theelectrode; and 5) the electrodes are expensive. Miles went on todescribe an electrode with a feature that would allow it to be anchoredat the insertion target location thus preventing movement postinsertion. J Siegfried (Siegried et al., “Intracerebral electrodeimplantation system.” Journal of Neurosurgery 59:356-359, 1983) alsodescribed an improved electrode along with a fixation device which couldsecure the electrode leadwire accurately with a fixture at the burr holelocation.

[0030] DBS and Essential Tremor

[0031] R. Tasker ((Tasker “Deep brain stimulation is preferable tothalamotomy for tremor suppression”, Surg. Neurol., 49:145-154, 1998)demonstrated that DBS is preferable to thalamotomy for tremorsuppression in that tremor recurrence after DBS can be controlled bystimulation parameter adjustment rather than by re-operation, butthalamotomy recurrence can only be corrected by secondary surgery.Additionally, ataxia, dysarthria and gait disturbance were more commonafter thalamotomy (42%) than in DBS (26%) and that when they occurredafter DBS they were nearly always controlled by adjusting stimulationparameters. J P Hubble (Hubble et al., “Deep brain stimulation foressential tremor”, Neurology, 46:1150-1153, 1996) demonstrated that DBSapplied in the left Vim thalamic nucleus could be applied for essentialtremor (ET) safely and effectively.

[0032] Upper Limb

[0033] R. G. Brown (Brown, et al., “Impact of deep brain stimulation onupper limb akinesia in Parkinson's disease”, Annals of Neurology,45(4)473-487, April 1999) has also shown that upper limb akinesia inParkinson's disease may be treated by DBS of the internal pallidum orsubthalamic nucleus.

[0034] Basic Research

[0035] R. Lansek (Lansek et al., “The monkey globus pallidus: neuronaldischarge properties in relation to movement”, Journal of Physiology301:439-455, 1980) demonstrated that the function of pallidal neuronesis intimately concerned with movement performance, as very discretemovements were represented by the discharges of individual neurons. ABenazzouz (Benazzouz et al., “Responses of substantia nigra parsreticulata and globus pallidus complex to high frequency stimulation ofthe subthalamic nucleus in rats: electrophysiological data”.Neuroscience Letters, 189:77-80, 1995) demonstrated that high frequencystimulation of the subthalamic nucleus (HFS-STN) induces a dear cutdecrease in neuronal activity in its two main efferents, the substantianigra pars reticulata (SNr) and entopeduncular nucleus (EP) in basicstudies in rats, thus providing an explanation for the alleviation ofParkinsonian symptoms by chronic STN stimulation in human patients.

[0036] R R Tasker (Tasker et al., “Investigation of the surgical targetfor alleviation of involuntary movement disorders”, Appl. Neurophysiol.,45:261-274, 1982) reviewed data from 198 stereotactic procedures withdata from 9,383 sites, concluding that a common target in inferior VIMin the 13.5 mm sagittal plane for the control of a variety ofdyskinesias existed.

[0037] From the above brief review of the literature, it is thus seenthat although much research has been done to date, there exists acritical need in the art for a DBS system that can specifically addressthe needs of individual patients in order to provide relief or treatmentfor various disorders.

SUMMARY OF THE INVENTION

[0038] The present invention addresses the above and other needs byproviding a deep brain stimulation (DBS) system that offers: (1) alonger operational life than has heretofore been available withimplanted electronic systems, (2) leads and electrodes specificallysuited for the DBS application, and (3) a multiplicity of stimulationchannels through which stimulation may be delivered deep within thebrain of the patient. The DBS system described herein advantageously ispowered by a rechargeable lithium-ion battery. The system has 4 channelsdriving 16 electrodes. The system is capable of providing many years ofoperation. The system may be easily programmed for use by a clinician,and further affords a simple but highly advanced control interfacethrough which the patient may easy change stimulation parameters withinacceptable limits.

[0039] In accordance with one aspect of the invention, a small,implantable pulse generator (IPG) forms a key component of the DBSsystem. Advantageously, the IPG used with the DBS system is small enoughto be implanted directly in the cranium of the patient, therebyeliminating the long lead wires and tunneling procedures that have beenrequired with existing DBS systems.

[0040] In accordance with another key aspect of the invention, the DBSsystem allows up to two electrode arrays to be attached to the IPG,thereby eliminating the requirement for implanting two independent IPG'sfor bilateral stimulation of deep brain structures.

[0041] It is a feature of the invention to provide a DBS system thatincorporates a replenishable power source, e.g., a rechargeable battery,as part of, or coupled to, an implanted pulse generator, whereby thepower source may be replenished, as required, in order to afford a longoperating life for the DBS system.

[0042] It is another feature of the invention, in accordance with oneembodiment thereof, to provide a DBS system that is capable ofdelivering stimulation pulses to the brain through selected electrodeson up to two electrode arrays connected to a single, multichannel pulsegenerator, whereby bilateral stimulation of the brain may be provided,if desired.

BRIEF DESCRIPTION OF THE DRAWINGS

[0043] The above and other aspects, features and advantages of thepresent invention will be more apparent from the following moreparticular description thereof, presented in conjunction with thefollowing drawings wherein:

[0044]FIG. 1 illustrates the various components of a deep brainstimulation (DBS) system made in accordance with the invention;

[0045]FIG. 2 is a block diagram of a DBS system of FIG. 1, andillustrates the various elements within each of the main sub-systems ofthe DBS system, which subsystems include an Implantable Pulse Generator(IPG), a Hand-Held Programmer (HHP), a Clinician's Programming System(CPS), a Manufacturing and Diagnostic System (MDS), and an ExternalBattery Charging System (ECBS); and

[0046]FIG. 3 is a block diagram of the IPG of FIG. 2.

[0047] Corresponding reference characters indicate correspondingcomponents throughout the several views of the drawings.

DETAILED DESCRIPTION OF THE INVENTION

[0048] The following description is of the best mode presentlycontemplated for carrying out the invention. This description is not tobe taken in a limiting sense, but is made merely for the purpose ofdescribing the general principles of the invention. The scope of theinvention should be determined with reference to the claims.

[0049] The DBS system of the present invention includes a craniummountable pulse generator, support for two electrode cables supportingbilateral brain stimulation, electrodes specifically designed for thesmall structures required for the DBS application, and an electrodefixation system guaranteeing reliable electrode and lead wire positiononce implanted.

[0050] A DBS system 10 made in accordance with the invention isillustrated in FIG. 1. The DBS system 10 includes an implantable pulsegenerator (IPG) 20 adapted to be implanted directly in or on the cranium16 of a patient. At least one lead 30, having a plurality of electrodes32 thereon, is attached to the IPG 20 via a suitable connector 22. Up totwo separate leads 30 may be attached to the IPG 20. Hence, FIG. 1 shows(in phantom lines) a second lead 30′ , having electrodes 32′ thereon,also attached to the IPG 20. Each lead includes at least two electrodes32, and may include as many as sixteen electrodes 32. A preferred IPG 20has four channels and can drive up to sixteen electrodes.

[0051] The IPG 20 includes a rechargeable battery. The battery isrecharged, as required, from an external battery charging system (EBCS)40, typically through an inductive link 42.

[0052] The IPG 20, as explained more fully below, includes a processorand other electronic circuitry that allows it to generate stimuluspulses that are applied to the patient through the electrodes 32 inaccordance with a stored program. The IPG 20 is programmed and testedthrough a hand held programmer (HHP) 50; a clinician programming system(CPS) 60 that uses an HHP, or equivalent, to relay information; or amanufacturing and diagnostic system (MDS) 70.

[0053] The HHP 50 may be coupled to the IPG 20 via an RF link 44.Similarly, the MDS 70 may be coupled to the IPG 20 via another RF link45. The CPS 60, which is coupled to the IPG 20 by way of the HHP 50, mayalso be coupled to the HHP 50 via an infra-red link 46. Likewise, theMDS 70 may be coupled to the HHP via another infra-red link 47. Othertypes of telecommunicative links, other than RF or infra-red may also beused for this purpose. Through these links, the CPS 60, for example, maybe coupled through the HHP 50 to the IPG 20 for programming ordiagnostic purposes. The MDS may also be coupled to the IPG 20, eitherdirectly through the RF link 45, or indirectly through the IR link 47with the HHP 50.

[0054] Turning next to FIG. 2, a block diagram of the DBS system 10 isillustrated, Including the various elements within each of the mainsub-systems of the DBS system. The subsystems of the DBS system 10include an Implantable Pulse Generator (IPG) 20, a Hand-Held Programmer(HHP) 50, a Clinician's Programming System (CPS) 60, a Manufacturing andDiagnostic System (MDS) 70, and an External Battery Charging System(ECBS) 40.

[0055] As seen in FIG. 2, the IPG 20 includes various elements,including a microprocessor 21, IPG firmware 22, a SRAM memory 23 (whichSRAM memory is optional, and may not be needed in some embodiments), aSEEROM memory 24, an analog IPG pulse generator integrated circuit (IC)25 (which analog pulse generator circuit 25 functions as the outputcircuit of the IPG), a digital IPG pulse generator IC 26, a rechargeablebattery 27, a battery charging system and telemetry circuit 28, and anRF telemetry circuit 29.

[0056] The microprocessor 21, in the preferred embodiment, comprises a16 bit microprocessor and associated external controller based upon theVAutomation 8086 processor, or equivalent. Advantageously, thisprocessor 21 is a flexible 16 bit processor that has been around foryears and was the processor used in the IBM PC, thus many developmenttools are available for both software and hardware design for thisdevice. The general performance-based features for the core and theadditional peripheral devices in the mircoprocessor IC 21 are summarizedas follows:

[0057] 1. Core, Equivalent to Intel 8086 from Vautomation, orequivalent.

[0058] 2. Operating Voltage: 2.2-3.5 V

[0059] 3. Oscillator—1.048 MHz crystal controlled oscillator, under 1 uAcurrent consumption, 2.2-3.5 V supply

[0060] 4. Address Bus: 20 bit, non-multiplexed

[0061] 5. Data Bus: 16 bit, non-multiplexed, supports multiplexed withCPU_ALE signal

[0062] 6. Power Consumption: 300 uA @ 1 MHz main crystal frequency

[0063] 7. Memory: ROM—1 Kbyte Mask ROM, containing bootstrap andinitialization routines; SRAM—16 Kbyte, used for program and data space

[0064] 8. External Memory: Provision for powering and reading from andwriting to Atmel SEEPROM for operating system and initial parameterstorage; Provision for None, 256 or 512 Kbytes external SRAM

[0065] 9. Analog to Digital Converter. 12 bit, 4 channel signalmultiplexer, 3 differential, 1 single-ended input signals, Vccmeasurement—warm-up in 1 mS, Conversion time: 550 clocks (successiveapproximation), Programmable range and offset, External VRH and VRL,Separate VDD connection

[0066] 10. Synchronous Serial Interfaces (2)—Clock and data in, clockand data out, handshake in and out

[0067] 11. Piezo Buzzer control—7 bit tone register, bipolar ormonopolar drive, 35568 Hz base block, tone is clock divided by 7 bitvalue in register, 8^(th) bit is on/off control

[0068] 12. Interrupt Control—3 external interrupt request lines, hightrue

[0069] 13. Invalid address detection non-maskable interrupt

[0070] 14. External I/O Device select, low true

[0071] 15. RF Telemetry; QFAST Modulation method with demodulator and RFmixer circuitry, Power control for external RF Circuitry, Antenna tuningcontrol: 4 bits, Device ID registers: 24 bit, Timing Control forautomatic receive, with clock pulse stealer circuitry for Time baseadjustment, Data rate 512 bits per second to 8192 bits per second

[0072] 16. Wakeup Timers: Timer 1-10 bit up-counter, 1 Hz drive, HIRQ oncompare to value, then reset and up count again, range of programmablevalues is 3 sec to 1026 seconds; Timer 2-12 bit up-counter, 8 Hz drive,HIRQ on compare to value, then reset and up count again; Timer 3-12 bitup-counter, 1024 Hz drive, HIRQ on compare to value, then reset andcount again

[0073] 17. One-Minute Counter—modulo 60 counter driven by 1 Hz and HIRQgenerator

[0074] 18. Time of Day Registers

[0075] 19. Watchdog monitor—Wakeup timer 1 interrupt signal is monitoredand if two successive HIRQ3 signals are detected without proper watchdogsupervision by the main processor then a system reset is asserted.

[0076] 20. LCD Clock—clock line for external LCD display (to be used inHHP)

[0077] 21. Test pins for system control bus visibility and debug

[0078] 22. General purpose 110 used for pump control, but useful forother functions

[0079] 23. Power On Clear Reset Circuitry

[0080] The RF telemetry circuit 29 utilized within the IPG 20, in onepreferred embodiment, is based on QFAST technology. QFAST stands for“Quadrature Fast Acquisition Spread Spectrum Technique”, and representsa known and viable approach for modulating and demodulating data. TheQFAST RF telemetry method is further disclosed in U.S. Pat. No.5,559,828, incorporated herein by reference. The QFAST methodologyutilizes an IIQ modulation and demodulation scheme that synchronouslyencodes clock and data onto a carrier signal of a suitable frequency,e.g., 262 KHz. The RF receive mixer and demodulator sections areimplemented almost entirely on the Processor IC with only externalreceive amplifier circuitry and an antenna required to supplement thecircuit. A method of tuning the antenna due to center frequency shiftsupon laser welding the enclosure around the processor hybrid isimplemented under software control. Pre-weld tuning is accomplished bythe use of binary capacitors (capacitor chip arrays which are wirebonded during fabrication and tuned by testing and creating wire bondsas needed).

[0081] The RF carrier is derived from the processor system clock. In oneembodiment, the system clock operates at 1.000 MHz. Other frequencyranges may be used, as needed. The data rate is adjustable by registercontrol over a suitable range, e.g., from 512 to 4096 bits per second,and the range of the link at 4 kb/s (kilobits/second) through an 8 milTitanium enclosure is greater than 40 inches.

[0082] Other components or elements within the IPG 20 may beconventional or as known in the art.

[0083] Still with reference to FIG. 2, the hand held programmer 50 isused by the patient to control the operation of the DBS ImplantablePulse Generator (IPG). The HHP functions as a small pager-like devicewhich is designed to control the IPG. The HHP, in one embodiment, uses a16 bit microprocessor 51 as its main controller. This microprocessor 51may be the same as the microprocessor 21, used within the IPG 20, andthus has all of the benefits and features described previously. Thefollowing is a summary of the features of the HHP 50:

[0084] 1. Package—central electronics volume is sealed against moistureingress. Battery compartment is moisture resistant. ESDprotection—Internal surfaces treated for ESD protection.Size—3.5″L×2.6″W×0.65″T; Shape—Landscape Pager.

[0085] 2. LCD: Pixel area—128 columns by 55 rows; ICON area—above pixelarea—time of day, month, date, activity Icon, battery warning, alarmwarning, reservoir volume (battery charge); Interface—SPI, IIC or 8 bitparallel—SPI implemented to SSI of ASIC; Programming—bit mapped graphicsinstruction set; Contrast hardware and software command; PowerConsumption<20 uA ICON, <500 uA pixel area on.

[0086] 3. Keyboard: Number of keys 5, one hidden; Action, any key cancause interrupt request, maskable; Seal/environmental—sealed to preventmoisture ingress, ESD shielded and debounced; Reset—Hardware reset ifall five keys pressed together

[0087] 4. Vibrator—A pager type vibrator motor is available fornon-audible alerts to the user—Power Consumption—<60 mA, Control—singlebit control

[0088] 5. Audio transducer—Performance—>75 db spl output at 2 KHz; PowerConsumption <10 mA, Control—7 bit register for tone control, 1 bit foron/off

[0089] 6. IRDA Port—115 Kbit/s fixed data rate, IRDA 1.2 low powerstandard compliant. Can be powered down, as can UART. IrDA port receiveline can be powered independently to see if external device needsattention even when UART is off.

[0090] 7. Batteries and upconversion—Main Battery: lithium primary;Expected Battery Life—preferably more than 60 weeks, but at least 2months at average current of 1 mA.

[0091] 8. Processor 8086 core ASIC—see specification for Processor ICand VAutomation specification Memory: 1 Kbyte boot ROM, 16 Kbyteinternal SRAM, 1 Mbyte External SRAM memory space, bank decoded into twopages, two 4 Mbit devices, accessible byte or wordwise; 512 K

[0092] 9. External SEEPROM—four 64 Kbyte devices at address 0, 1, 2, 3.

[0093] The HHP 50 is designed to support multiple languages through theuse of its graphics LCD and to display continuously basic statusinformation about the implanted device and its own operation. The HHP 50can perform RF telemetry to the IPG at the specifications mentionedabove, as well as communicate over an IrDA 1.2 compatible infraredcable-less data link at 115 Kbaud over a 30 cm range. This range can beextended with the use of a commercially available IrDA 1.2 compliantserial port 8 foot expander which plugs into the 9 pin Sub-D connectorfound on personal computers and terminates with an IrDA transceiver.

[0094] As can be seen in FIG. 2, the DBS system 10 includes four majorfunctional blocks: the Implanted Pulse Generator (IPG) 20; The Hand-HeldProgrammer (HHP) 50; The External Battery Charging System (EBCS) 40; andthe Clinician's Programming System (CPS) 60. As previously indicated,the IPG 20 contains a 16 bit microprocessor 21, memory 23 and 24, arechargeable battery 27 and custom pulse generation circuitry 25 and 26.Communication to the IPG 20 is via RF link 44 or other links 42 or 45.The HHP 50 takes the form of a small pager-like device, with an LCDgraphics display and a simple and direct user interface and keyboard.The HHP 50 is able to communicate with the IPG 20 over a comfortabledistance, e.g., up to 2 feet away, allowing the patient and clinicianalike simple and efficient control of the IPG.

[0095] The CPS 60 is used by the clinician to fit the IPG 20 andelectrodes 32 to the patient, and to record and document all stimulationsettings. The CPS 60 communicates to the HHP 50 using an InfraRedwireless link 46, a standard in the computer industry. The HHP 50communicates to the IPG 20 over an RF link 44. Secure communicationswithout error are provided by utilizing a 24 bit identification code forall components in the system along with error detection codes embeddedin all data packets submitted by any device in the system.

[0096] The HHP 50, in one embodiment, utilizes a label and membranekeypad to adapt to DBS applications. Software applicable to OBS is alsoused. The HHP 50 represents a general-purpose 8086-based productplatform. Such platform is extremely flexible, yet meets the needs ofsmall weight and size, rugged environmental protections and ease of usefor the DBS application.

[0097] The packaging of the implanted pulse generator (IPG) 20 and itslead(s) 30 and electrodes 32 and electrode leadwire fixation systemrepresent an important part of the system. A distally-located pulsegenerator has the luxury of available volume in which to house itspower, electronics and control systems. A cranium mounted system,however, is greatly restricted in volume and depth. Yet, the IPG 20 hasall of the features deemed important to the application within thevolume constraints described.

[0098] The key features of the DBS system 10 shown in FIGS. 1 and 2 aresummarized below:

[0099] 1. DBS Implantable Pulse Generator (IPG) Features:

[0100] a. 4 to 16 electrode contacts.

[0101] b. 4 channels, comprised of any combination within the 16contacts.

[0102] c. Individual cathode and anode amplitude control.

[0103] d. Rechargeable battery.

[0104] e. Tool-less connector.

[0105] f. Small package.

[0106] 2. DBS Pulse Generator Performance—Rechargeable Battery

[0107] a. Inductively charged from 2-3 cm.

[0108] b. 80% charged in 4 hours.

[0109] c. At 10 yrs, 1 channel typical discharge in approximately 30days; 4 channels typical discharge approximately 7 days.

[0110] d. IPG battery status monitoring with telemetry to hand heldprogrammer (HHP).

[0111] e. Battery control and safety circuitry for 100% failsafeoperation.

[0112] 3. DBS Pulse Generator Performance—Stimulation Capability

[0113] a. Up to 16 electrodes and case ground, individually controlled:biphasic pulse current, frequency, pulse width, channel assignment,monopolar or multipolar operation.

[0114] b. Up to 4 Channels: channel=common frequency and pulse durationfor channel assigned electrodes (electrodes can operate in up to fourchannels).

[0115] c. Amplitude: each electrode: 0-12 mA cathodic or anodic currentin discrete steps, e.g., steps of 0.1 mA. Simultaneous output: ±20 mA(distributed)

[0116] d. Pulse Width: 25 μs (microseconds) to 1 ms (millisecond), in 10μs steps (equal for electrodes on a channel).

[0117] e. Rate: 2 ranges including normal, 0-150 pps per channel inapproximately 1 pps steps, and high rate (1 channel) 160-1200 inapproximately 10 pps steps.

[0118] f. Channel Timing: channel rates are regulated to prevent overlapwith a method that is transparent to the patient.

[0119] g. Anode Control: 3 modes-monopolar case (any electrode(s) (−) tocase), passive anodes (electrodes connected to ground), and active anodewith individual amplitude control.

[0120] h. Charge Balance: assured through capacitor interface betweenelectrode and output circuitry.

[0121] i. Soft Start: from 1 to 10 seconds, in 1 second steps.

[0122] j. Run Schedule: all channels of the implant turn on and off tothe last stimulation settings at preset programmed times.

[0123] k. Impedance: monopolar at 4 mA: 500 Ohms typical.

[0124] 4. DBS Pulse Generator Performance—Telemetry Output

[0125] a. Battery Capacity: automatic telemetry data retrieval initiatedby external programmer communication.

[0126] b. Electrode Impedance: automatic telemetry data retrievalinitiated by external programmer communication.

[0127] c. Confirmations: programmable parameter changes from externalequipment confirmed with back telemetry.

[0128] d. Programmed Settings: automatic telemetry data retrieval of allprogrammable settings initiated by external programmer communication.

[0129] 5. DBS Pulse Generator Performance—Connector

[0130] a. Two feedthroughs with up to 16 total electrical contacts for aremovable lead system with strong, reliable electrical performance (lowcurrent spread) under implanted conditions.

[0131] b. Although the connection is typically made only once for anydevice, the connector mechanism is designed to withstand a minimum of 10connections.

[0132] c. The lead connector system utilizes a simple method to securethe electrode leadwire without the use of a tool.

[0133] 6. DBS Patient Programmer Features

[0134] a. Intuitive user interface.

[0135] b. Back-lighted flat panel screen.

[0136] c. Hidden physician screen.

[0137] d. 2-3 foot RF range.

[0138] e. Implant battery monitor.

[0139] f. Run time scheduler.

[0140] g. 4 program storage.

[0141] h. Infrared communication link to clinician's programming system.

[0142] A block diagram showing the hybrid configuration of the IPG 20 inaccordance with a preferred embodiment of the invention is shown in FIG.3. As seen in FIG. 3, the microprocessor 21 lies at the heart of theIPG. RF telemetry TXIRX Circuits 29 interface with the processor 21.Included in the telemetry circuits 29 are an antenna, impedance matchingtuning amplifier, and the like.

[0143] SRAM memory 23, when used, and SEEROM memory 24 provide storagefor data and control signals associated with the operation of theprocessor 21.

[0144] The processor 21 controls digital IC 26 and directs it togenerate appropriate stimulation currents for delivery through the leads30 and 30′ and electrodes 32 and 32′. The digital IC 26, in turn,controls analog IC 25 so as to generate the stimulus currents.Connection with the lead(s) 30, 30′ is made through a capacitor array,so that all electrodes are capacitor coupled. A header connector 22facilitates detachable connection of the lead(s) 30, 30′ with the IPG20.

[0145] A rechargeable battery 27, e.g., a lithium-ion battery, powersoperation of the IPG 20. A charger coil 19 provides a means for couplingenergy into the battery for recharging. Battery charger and protectioncircuits 28 receive the power for recharging the battery through thecharger coil 19; regulate and distribute power to the rest of the IPG20, as required, and monitor the status of the rechargeable battery 27.

[0146] While the invention herein disclosed has been described by meansof specific embodiments and applications thereof, numerous modificationsand variations could be made thereto by those skilled in the art withoutdeparting from the scope of the invention set forth in the claims.

What is claimed is:
 1. A multichannel deep brain stimulation system (10)comprising: an implantable pulse generator (20) connected to at leastone electrode array (30), said at least one electrode array having aplurality of electrodes (32) through which electrical stimuli may beapplied to body tissue; a rechargeable battery (27) coupled to theimplantable pulse generator; a hand-held programmer (50); and anexternal battery charging system (40); wherein the implantable pulsegenerator (20) and at least one electrode array (30) are adapted to beimplanted directly in the cranium of a patient, whereby electricalstimuli may be applied to brain tissue of the patient; and wherein theimplantable pulse generator (20) includes control circuits (21, 26, 27)and memory circuits (22, 24) that cause stimulation pulses to be appliedthrough at least one of a plurality of channels to the electrodes (32)of the at least one electrode array in accordance with a program storedwithin the memory circuits of the implantable pulse generator; andwherein the hand-held programmer (50) may be coupled to the implantablepulse generator through an RF link (44) for the purpose of programmingand testing the implantable pulse generator (20); and wherein theexternal battery charging system (40) may be inductively coupled to therechargeable battery (27) for the purpose of replenishing the powerstored within the rechargeable battery.
 2. The deep brain stimulationsystem of claim 1 further including a manufacturing and diagnosticsystem (70), the manufacturing and diagnostic system including means forcoupling with the implantable pulse generator (20) through an RF link(45).
 3. The deep brain stimulation system of claim 2 wherein themanufacturing and diagnostic system (70) further includes means forcoupling with the hand-held programmer (50) through an infra-red link(47).
 4. The deep brain stimulation system of claim 1 wherein at leasttwo electrode arrays (30, 30′) are attached to the implantable pulsegenerator (20), thereby facilitating bilateral stimulation of the brainof the patient.
 5. The deep brain stimulation system of claim 5 whereineach of the electrode arrays (30 and 30′) includes at least two and asmany as sixteen electrodes (32, 32′).
 6. The deep brain stimulationsystem of claim 1 further including a clinician programmer (60), andwherein the clinician programmer (60) may be coupled to the hand-heldprogrammer (50) through an infra-red link (46) for the purpose ofcoupling the clinician programmer with the implantable pulse generator(20).
 7. The deep brain stimulation system of claim 1 wherein the atleast one electrode array (30) is detachably connected to theimplantable pulse generator (20) through a header connector (22).
 8. Thedeep brain stimulation system of claim 7 wherein the at least oneelectrode array (30) is capacitively coupled to an output circuit (25)of the implantable pulse generator.
 9. A multichannel bilateral deepbrain stimulation system (10) comprising: an implantable pulse generator(20) detachably connected to a plurality of electrode arrays (30, 30′),each of said plurality of electrode arrays having a plurality ofelectrodes (32) thereon through which electrical stimuli may be appliedto body tissue; processing means (21, 26, 27) and memory circuits (22,24) included within the implantable pulse generator that causestimulation pulses to be applied to selected electrodes (32) of theplurality of electrode arrays in accordance with a stimulation programstored within the memory circuits; a rechargeable battery (27) includedwithin the implantable pulse generator that provides operating power forthe implantable pulse generator; means (50) for non-invasivelyprogramming the memory circuits with a desired stimulation program: andmeans (40) for non-invasively recharging the rechargeable battery.